Biopolymer arrays such as polynucleotide arrays (for example, DNA or RNA arrays), are known and are used, for example, as diagnostic or screening tools. Such arrays include regions of usually different sequence polynucleotides arranged in a predetermined configuration on a substrate. These regions (sometimes referenced as “features”) are positioned at respective locations (“addresses”) on the substrate. The arrays, when exposed to a sample, will exhibit an observed binding pattern. This binding pattern can be detected upon interrogating the array. For example all polynucleotide targets (for example, DNA) in the sample can be labeled with a suitable label (such as a fluorescent compound), and the fluorescence pattern on the array accurately observed following exposure to the sample. Assuming that the different sequence polynucleotides were correctly deposited in accordance with the predetermined configuration, then the observed binding pattern will be indicative of the presence and/or concentration of one or more polynucleotide components of the sample.
Biopolymer arrays can be fabricated by depositing previously obtained biopolymers onto a substrate, or by in situ synthesis methods. The in situ fabrication methods include those described in U.S. Pat. No. 5,449,754 for synthesizing peptide arrays, and in U.S. Pat. No. 6,180,351 and WO 98/41531 and the references cited therein for synthesizing polynucleotide arrays. Further details of fabricating biopolymer arrays are described in U.S. Pat. Nos. 6,242,266, 6,232,072, 6,180,351, and 6,171,797. Other techniques for fabricating biopolymer arrays include known light directed synthesis techniques.
In array fabrication, the probes formed at each feature usually are expensive. Additionally, sample quantities available for testing are usually also very small and it is therefore desirable to simultaneously test the same sample against a large number of different probes on an array. These conditions make it desirable to produce arrays with large numbers of very small (for example, in the range of tens or one or two hundred microns), closely spaced features (for example many thousands of features). After an array has been exposed to a sample, the array is read with a reading apparatus (such as an array “scanner”), which detects the signals (such as a fluorescence pattern) from the array features. Such a reader should typically have a very fine resolution (for example, in the range of five to twenty microns).
The signal image resulting from reading the array can then be digitally processed to evaluate which regions (pixels) of read data belong to a given feature as well as the total signal strength from each of the features. The foregoing steps, separately or collectively, are referred to as “feature extraction”. However, the signal in the image for any particular feature may be very low. Additionally, the results obtained by an array reader have inherent limitations governed by the reader's performance characteristics which affect how the read results are interpreted. For example, a low accuracy in a detected signal (as may result from high noise in the reader) may lead a user who is trying to interpret read results from an array (or software performing such a task) to conclude that the result (in the form of a detected signal) from a particular feature is unreliable where the detected signal from that feature is already low. This may lead to discarding the read result from that particular feature. The present invention recognizes though, that often results from reading chemical arrays are shared for others to evaluate. However, as the present invention further recognizes, shared results alone without an understanding of the performance characteristics of the reader which obtained them can lead to a misinterpretation of those results. For example, a user in the previous example having only the results from the reading, would not know that the result from the low signal feature should be discarded. This can lead to misinterpretation of the results from the read array with serious consequences in research or diagnosis.
The present invention recognizes then that it would be desirable to ensure that one or more performance characteristics of a chemical array reader are readily available along with the results from reading an array on that reader.